title: A lipid-signaled myosin phosphatase surge disperses cortical contractile force early in cell spreading.
abstract: When cells cease migrating through the vasculature, adhere to extracellular matrix, and begin to spread, they exhibit rapid changes in contraction and relaxation at peripheral regions newly contacting the underlying substrata. We describe here a requirement in this process for myosin II disassembly at the cell cortex via the action of myosin phosphatase (MP), which in turn is regulated by a plasma membrane signaling lipid. Cells in suspension exhibit high levels of activity of the signaling enzyme phospholipase D2 (PLD2), elevating production of the lipid second messenger phosphatidic acid (PA) at the plasma membrane, which in turn recruits MP and stores it there in a presumed inactive state. On cell attachment, down-regulation of PLD2 activity decreases PA production, leading to MP release, myosin dephosphorylation, and actomyosin disassembly. This novel model for recruitment and restraint of MP provides a means to effect a rapid cytoskeletal reorganization at the cell cortex upon demand.
authors.affiliation: Department of Pharmacology and Center for Developmental Genetics, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Du
authors.forename: Michael A
authors.initials: MA
authors.lastname: Frohman
mesh_terms: D000577:Amides / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D004791:Enzyme Inhibitors / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000235:genetics / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D034622:RNA Interference; D015290:Second Messenger Systems / Q000502:physiology*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D008055:Lipids; D010712:Phosphatidic Acids; D011725:Pyridines; C108830:Y 27632; C472645:blebbistatin; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase; C105606:phospholipase D2; D010739:Phospholipase D; D024462:Myosin Type II